5-HT1 agonists are known for their ability to cause vasoconstriction of dilated cranial and basilar arteries. NSAIDs are known for their ability to treat pain. The combination of these two classes of drugs has been used to treat migraine headaches in humans (U.S. Pat. Nos. 7,332,183; 6,060,499; 5,872,145; 6,384,034; U.S. Patent Application No. 2002/0099059; EP 1051993; EP 1064967; EP 1051995; EP 1064966; EP 1064948; and Brandes J L et al (2007), “Sumatriptan-naproxen for acute treatment of migraine: a randomized trial”, JAMA 297(13):1443-54).
5-HT1 agonists are generally administered orally, intranasally or parenterally (U.S. Pat. Nos. 4,493,830; 4,532,244; 4,816,470; 5,307,845; 5,307,953; 5,554,639; 5,705,520; 6,368,627; and WO 00/06161).
NSAIDs are generally administered orally, for example as a single or multilayer tablet or coated granule dosage form (U.S. Pat. Nos. 6,365,184; 5,637,320; 5,480,650; and 6,387,410).
U.S. Pat. No 7,332,183 discloses a multilayer tablet for a combination of naproxen or pharmaceutically acceptable salt thereof with a triptan. The composition is formulated so that each drug is contained in separate layers located side-by-side so that each dissolves independently of the other. Thus the formulation is said to overcome difficulties associated with the poor in vivo solubility of NSAIDs in conditions of low pH found in the stomach, specifically that the slow eroding nature of NSAIDs may cause the triptan to become entrapped and thereby delay release of the triptan. The manufacturing process necessary to prepare and maintain the actives in separate layers requires specialised equipment and/or processing techniques. This adds to the time and cost for the manufacture of the product.
Bansal P. et al (1994), Drug Development and Industrial Pharmacy, 20(13), pp. 2151-6 discusses the effect of water and mixing time on a composition comprising naproxen sodium and pharmaceutically acceptable excipients. They disclose that naproxen sodium appears to form a pseudo-polymorph when granulated in the presence of water affecting the dissolution time of the resultant composition. The effect is also emphasised by an increase in the mixing time during wet granulation.
A simplified pharmaceutical composition and dosage form is required whereby the adverse effects of the combination of these classes of drugs and processing limitations are overcome.